Patients with chronic rotator cuff tears frequently have anterior shoulder pain attributed to the long head of the biceps brachii (LHBB) tendon. In this study, tenodesis or tenotomy samples and cadaveric controls were assessed by use of immunohistochemical and histologic methods to quantify inflammation, vascularity, and neuronal plasticity. Patients had moderate pain and positive results on at least 1 clinical test of shoulder function. The number of axons in the distal LHBB was significantly less in patients with biceps tendinitis. Calcitonin gene-related peptide and substance P immunostaining was predominantly within nerve roots and blood vessels. A moderate correlation (R = 0.5) was identified between LHBB vascularity and pain scores. On the basis of these results, we conclude that, in the context of rotator cuff disease, the etiology of anterior shoulder pain with macroscopic changes in the biceps tendon is related to the complex interaction of the tendon and surrounding soft tissues, rather than a single entity.